Proposed model indicating that distinct subsets of CML LICs are supported by the IL-2/CD25 axis. Both CD25⁺FcεRIα⁻Lin⁻Sca-1⁺c-Kit⁺ (F⁻LSK) cells and CD25⁻F⁻LSK cells possess CML LIC activities and can interconvert each other. CD25⁺F⁻LSK cells are also capable of differentiating into mast cells, and cycle faster than the CD25⁻ counterpart. Microenvironment produced IL-2 can act on CD25⁺F⁻LSK cells, which further produce TGF-β to support self-renewal of both CD25⁺ and CD25⁻ CML LICs. See supplemental Figure 16 in the article by Kobayashi et al that begins on page 2540.